Abstract
Glioblastoma is aggressive, highly infiltrating, and the most frequent malignant form of brain cancer. With a median survival time of only 14.6 months, when treated with the standard of care, it is essential to find new therapeutic options. A specific CDK4/6 inhibitor, PD0332991, obtained accelerated approval from the Food and Drug Administration for the treatment of patients with advanced estrogen receptor-positive and HER2-negative breast cancer. Common alterations in the cyclin D1-cyclin-dependent kinase 4/6-retinoblastoma 1 pathway in glioblastoma make PD0332991 also an interesting drug for the treatment of glioblastoma. Promising results in in vitro studies, where patient derived glioblastoma cell lines showed sensitivity to PD0332991, gave motive to start in vivo studies. Outcomes of these studies have been contrasting in terms of PD0332991 efficacy within the brain: more research is necessary to conclude whether CDK4/6 inhibitor can be beneficial in the treatment of glioblastoma.
Highlights
Glioblastoma (GBM, Astrocytoma grade IV) is an aggressive, highly infiltrating form of brain cancer
The cyclin D1-cyclin-dependent kinase 4/6retinoblastoma 1 signaling pathway covers an important checkpoint in the cell cycle [6]
In 2010, compared Rb1-deficient to Rb1-proficient cell lines for differences in PD0332991 treatment response, whereby, in most cell lines, knockdown of Rb1 resulted in failure to stop proliferation through CDK4/6 inhibition [24]
Summary
Glioblastoma (GBM, Astrocytoma grade IV) is an aggressive, highly infiltrating form of brain cancer. With an incidence rate of 3.19 per 100,000 in the US, it occurs over 21 times less often than breast cancer [2, 3]. The standard of care for glioblastoma consists of surgical resection followed by radiotherapy in combination with temozolomide [4]. Significant improvements to the standard treatment leading to overall survival extension have been lacking. This devastating disease has a median survival time of only 14.6 months [4]. It is, essential to find new therapeutic options. This review focuses on the data on PD0332991 (Palbociclib) studies in glioblastoma and how this drug can play a role in glioblastoma treatment
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